A central role for serum lipids in the pathogenesis of vascular disease has long been postulated, but has remained an illusive problem for both the biochemist and the clinician. Since 1955, it has been known that prebeta lipoproteinemia is an early finding in ischemic heart disease and a constant finding in maturity-onset diabetes where vascular disease is a familiar part of the pathological process. The present investigation has posed two linking hypotheses from the last 6 1/2 years of investigation into the metabolism of this lipoprotein and its relationship to carbohydrate physiology: 1) Abnormalities of metabolism of the protein moiety associated with the circulating lipoprotein may be central to the pathophysiology of prebeta lipemia. 2) An hormonal basis for the lipemia with a relative excess of insulin and/or deficiency of glucagon "activity" may represent the initiating factors which alter carrier protein metabolism. If this sequence of events represents the mechanism and pathophysology of some forms of human lipoprotein disease, then the implications in terms of diagnosis and therapy are clear. Finally, the elucidation of lipoprotein-carbohydrate-hormone interrelationships should importantly add to the present state of knowledge concerning intermediary metabolism. BIBLIOGRAPHIC REFERENCES: Eaton, R. Philip. 1976. Incorporation of Se75 Selenomethionine into Human Apoproteins. I. Characterization of Specificity in Very-Low-Density and Low-Density Lipoproteins. Diabetes 25: 37-44. Eaton, R. Philip, S. Crespin, David Kipnis. 1976. Incorporation of Se75 Selenomethionine into Human Apoproteins. II. Characterization of Metabolism of Very-Low-Density and Low-Density Lipoproteins in vivo and in vitro. Diabetes 25: 44-51.